Henderson Gregory C, Dhatariya Ketan, Ford G Charles, Klaus Katherine A, Basu Rita, Rizza Robert A, Jensen Michael D, Khosla Sundeep, O'Brien Peter, Nair K Sreekumaran
Division of Endocrinology, Mayo Clinic, Rochester, MN 55905, USA.
FASEB J. 2009 Feb;23(2):631-41. doi: 10.1096/fj.08-117200. Epub 2008 Sep 30.
We investigated age and sex effects and determined whether androgen replacement in elderly individuals (> or = 60 yr) could augment protein synthesis. Thirty young men and 32 young women (18-31 yr) were studied once, whereas 87 elderly men were studied before and after 1 yr of treatment with 5 mg/day testosterone (T), 75 mg/day dehydroepiandrosterone (DHEA), or placebo (P); and 57 elderly women were studied before and after 1 yr of treatment with 50 mg/day DHEA or P. [(15)N]Phenylalanine and [(2)H(4)]tyrosine tracers were infused, with measurements in plasma and vastus lateralis muscle. Whole-body protein synthesis per fat-free mass and muscle protein fractional synthesis rate (FSR) were lower in elderly than in young individuals (P<0.001), not significantly affected by hormone treatments, and higher in women than in men (P<0.0001), with no sex x age interaction. In regression analyses, peak O2 consumption (VO2peak), resting energy expenditure (REE), and sex were independently associated with muscle FSR, as were VO2peak, REE, and interactions of sex with insulin-like growth factor-II and insulin for whole-body protein synthesis. Women maintain higher protein synthesis than men across the lifespan as rates decline in both sexes, and neither full replacement of DHEA (in elderly men and women) nor partial replacement of bioavailable T (in elderly men) is able to amend the age-related declines.
我们研究了年龄和性别效应,并确定老年个体(≥60岁)雄激素替代治疗是否能增强蛋白质合成。对30名年轻男性和32名年轻女性(18 - 31岁)进行了单次研究,而对87名老年男性在接受5毫克/天睾酮(T)、75毫克/天脱氢表雄酮(DHEA)或安慰剂(P)治疗1年前后进行了研究;对57名老年女性在接受50毫克/天DHEA或P治疗1年前后进行了研究。输注[(15)N]苯丙氨酸和[(2)H(4)]酪氨酸示踪剂,并在血浆和股外侧肌中进行测量。老年个体每无脂肪体重的全身蛋白质合成和肌肉蛋白质分数合成率(FSR)低于年轻个体(P<0.001),不受激素治疗的显著影响,女性高于男性(P<0.0001),且不存在性别×年龄交互作用。在回归分析中,峰值耗氧量(VO2peak)、静息能量消耗(REE)和性别与肌肉FSR独立相关,VO2peak、REE以及性别与胰岛素样生长因子-II和胰岛素的相互作用与全身蛋白质合成也独立相关。在整个生命周期中,随着两性合成率下降,女性的蛋白质合成维持在高于男性的水平,并且无论是DHEA的完全替代(老年男性和女性)还是生物可利用T的部分替代(老年男性)都无法改善与年龄相关的下降。